Approximately 185,000 individuals in the U.S. undergo an amputation each year. The majority of new amputations result from vascular disorders such as diabetes, with other causes including cancer and trauma. Almost all amputees (95%) have intense pain during the recovery period following their amputation, either sensed in the portion of the limb that remains (residual limb pain) or in the portion of the limb that has been removed (phantom pain). It is critical to treat this sub-chronic pain condition quickly and effectively to avoid the significant social, economic, and rehabilitation issues associated with severe post-amputation pain. Other types of neuropathic pain affect over 6 million Americans.
Almost all amputees (95%) have pain related to their amputation: approximately 68-76% of amputees have residual limb pain (RLP) and 72-85% of amputees have phantom limb pain (PLP). Their severity and prevalence make them significant medical problems. Pain can lead to discouragement, anger, depression, and general suffering. PLP and RLP frequently cause further disability and greatly reduce quality of life (QOL). In amputees with severe pain, it is frequently the pain rather than the loss of a limb that most impacts daily activities and employment. Amputee pain has a significant economic impact on the patient and society. For the patient, the median cost of medications exceeds $3,000/year and the median cost for a treatment regimen provided by a pain management center is over $6,000/year. The annual cost in the U.S. to manage post-amputation pain is estimated to be over $1.4 billion for medications and over $2.7 billion for pain center treatment programs. When the overall costs of pain management care are summed, the annual cost can exceed $30,000/patient for a cost of over $13 billion/year to treat amputees with severe pain in the US.
Present methods of treatment are unsatisfactory in reducing pain, have unwanted side effects, and are not suited for temporary use. Electrical stimulation of nerves can provide significant (>50%) pain relief, but present methods of implementation are either inappropriate for sub-chronic pain due to their invasiveness, or are uncomfortable and inconvenient to use. We have developed an innovative, minimally invasive method of delivering temporary electrical stimulation to target nerves. Preliminary data on treating amputee pain using methods according to the present invention are promising, but there is a significant need for a stimulation system that overcomes the technical and clinical barriers of presently available devices, including imprecise programming (requiring precise lead placement which is impractical for widespread use) and lack of moisture ingress protection (requiring removal of system during some daily activities).
PLP and RLP are severe and debilitating to a large proportion of amputees, who often progress through a series of treatments without finding relief. Most patients are managed with medications. Non-narcotic analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDS), are commonly used but are rarely sufficient in managing moderate to severe pain. Trials of narcotics have failed to show significant reduction in PLP, and they carry the risk of addiction and side effects, such as nausea, confusion, vomiting, hallucinations, drowsiness, headache, agitation, and insomnia. Other medications such as antidepressants are used for neuropathic pain, but their use for post-amputation pain is based primarily on anecdotal evidence and there are few controlled clinical trials to support their efficacy for post-amputation pain. Physical treatments (e.g., acupuncture, massage, heating/cooling of the residual limb) have limited data to support their use and are not well accepted. Psychological strategies, such as biofeedback and psychotherapy, may be used as an adjunct to other therapies but are seldom sufficient on their own, and there are few studies demonstrating their efficacy. Mirror-box therapy has demonstrated mixed results and is not widely used. Few surgical procedures are successful and most are contraindicated for the majority of the amputee patients 11. Studies have shown that pain resolves over the first 6 months following amputation for some patients. Within 6 months, RLP resolves for 60% of patients and PLP resolves for 10% of patients, with another 40% experiencing a significant reduction in pain intensity, making it inappropriate to use invasive methods before establishing that the pain is long-term (>6 months).
Prior electrical stimulation has been attempted. Transcutaneous electrical nerve stimulation (TENS, i.e., surface stimulation) is a commercially available treatment and has been demonstrated at being at least partially successful in reducing post-amputation pain. However, TENS has a low (<25%) success rate due to low patient compliance. Patients are non-compliant because the stimulus intensity required to activate deep nerves from the skin surface can activate cutaneous pain fibers leading to discomfort, the electrodes must be placed by skilled personnel daily, and the cumbersome systems interferes with daily activities. Spinal cord stimulation (SCS), motor cortex stimulation, and deep brain stimulation (DBS) have evidence of efficacy, but their invasiveness, high cost, and risk of complications makes them inappropriate for patients who may only need a temporary therapy. High frequency nerve block has been shown to decrease transmission of pain signals in the laboratory, but the therapy has not been developed for clinical use. Historically, peripheral nerve stimulation (PNS) for pain has not been widely used due to the complicated approach of dissecting nerves in an open surgical procedure and placing leads directly in contact with these target nerves. Such procedures are time consuming and complex (greatly limiting clinical use outside of academic institutions), have risks of damaging nerves, and often (27%) have electrode migration or failure. Other groups are developing percutaneous electrode placement methods, but their methods still require delicate, placement and intimate contact with the nerve, making them prone to complications and migration (up to 43%) because the technology lacks sufficient anchoring systems, leading to loss of pain relief and rapid failure (averaging 1-2 revisions/patient).